The present invention is directed to liposomes. More particularly, the present invention is directed to multilamellar vesicles having improved trapping efficiency and equilibrium transbilayer solute distribution.
Liposomes of the type which are multilamellar vesicles (MLV's) are usually formed by mechanical dispersion of dried lipid in an aqueous buffer. It is commonly assumed that this procedure results in an equilibrium interlamellar distribution of solutes present in the buffer. However, it has been demonstrated that the trapped buffer may have reduced solute concentrations resulting in osmotic imbalances between exterior and interior environments. Gruner et al., Biochemistry, 24, 2833-2842 (1985). These osmotic imbalances can lead to membrane potentials, transbilayer pH gradients and deformations due to osmotic forces. Equilibrium solute distributions can be achieved by techniques involving dispersion of the lipid in mixtures of organic solvent and aqueous buffer, where the organic solvent is subsequently removed under reduced pressure.
Alternative procedures have been described in U.S. Pat. No. 4,522,803 and copending U.S. patent applications Ser. Nos. 476,496 and 521,176, and incorporated herein by reference, to prepare liposomes having properties different than MLV's.
The low trapping volume and trapping efficiency of MLV systems have presented difficulties in employing these systems in applications such as drug delivery. As a result, alternative procedures have been developed to prepare liposomal systems which involve the use of organic solvents or detergents as solubilizing agents. Organic solvents and detergents are undesirable ingredients in drug delivery systems.
It would, therefore,-be desirable to obtain a multilamellar vesicle having high trapping efficiency, high trapped volumes and equilibrium transbilayer solute distribution prepared in the absence of organic solvents or detergents.